Takayuki Harada1, Chikako Harada. 1. Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu 183-8526, Japan.
Abstract
PURPOSE: Recent studies have demonstrated the mechanism of neural cell death, neuroprotection, and regeneration. However, the functional importance of glial cells during retinal degeneration is not well understood. In this review, we summarize our recent progress regarding the function of glial cells in neurotrophic factor production and neural cell death during retinal degeneration. METHODS: We made a rat model of photoreceptor degeneration by continuous light exposure, and examined the distribution and expression levels of neurotrophins and their receptors. In addition, we carried out quantitative analysis of neurotrophic factor production in cultured Müller glial cells and microglia. RESULTS: In the light-degenerated retina, microglia invade the photoreceptor layer from the inner part of the retina and increase the production of nerve growth factor (NGF). NGF decreases the production of basic fibroblast growth, factor, which prevents photoreceptor cell death, in Müller glial cells through low-affinity neurotrophin receptor p 75. Blockade of p 75 decreased photoreceptor cell death during light-induced retinal degeneration. CONCLUSIONS: These results suggest that a gliaglia network plays a critical role in neural cell death during retinal degeneration. Thus, a glia-glia network as well as a glia-neuron network could be a possible therapeutic target for inhibition of retinal degeneration.
PURPOSE: Recent studies have demonstrated the mechanism of neural cell death, neuroprotection, and regeneration. However, the functional importance of glial cells during retinal degeneration is not well understood. In this review, we summarize our recent progress regarding the function of glial cells in neurotrophic factor production and neural cell death during retinal degeneration. METHODS: We made a rat model of photoreceptor degeneration by continuous light exposure, and examined the distribution and expression levels of neurotrophins and their receptors. In addition, we carried out quantitative analysis of neurotrophic factor production in cultured Müller glial cells and microglia. RESULTS: In the light-degenerated retina, microglia invade the photoreceptor layer from the inner part of the retina and increase the production of nerve growth factor (NGF). NGF decreases the production of basic fibroblast growth, factor, which prevents photoreceptor cell death, in Müller glial cells through low-affinity neurotrophin receptor p 75. Blockade of p 75 decreased photoreceptor cell death during light-induced retinal degeneration. CONCLUSIONS: These results suggest that a gliaglia network plays a critical role in neural cell death during retinal degeneration. Thus, a glia-glia network as well as a glia-neuron network could be a possible therapeutic target for inhibition of retinal degeneration.